The basic objective of this research is the elucidation of the mechanisms of cell transformation induced by avian oncogenic viruses. Special emphasis will be placed on the oncogenes whose functions are related to early steps of signal transduction pathways. As representatives, we will focus our efforts on the activities of the Src family of tyrosine kinases and small molecular weight proteins containing only SH2/SH3 domains. Biochemical analysis of cell transformation by tyrosine kinase genes includes the mechanisms of regulation of c-Src kinase, particularly how its kinase activity is regulated by another kinase and by phosphatases, and the role of the Ras protein in src-induced transformation, and the role of serine/threonine protein kinases as effectors of the v-Src kinase. To understand how a small protein containing only SH2 and SH3 domain can cause cell transformation, we will analyze the specificity of the interactions between SH2 domains and phosphotyrosine-containing proteins, structures involved in the interactions, the significance of the small SH2 containing proteins in protection of tyrosine phosphorylated proteins from phosphatases, and the identification and characterization of activated kinases and its substrates in transformed cells. We will also investigate the possible interactions between small SH2/SH3 proteins and growth factor receptors, other known signal transduction proteins, and the role of Crk and other related proteins in induction of cell proliferation. Finally, we will characterize the product of a new receptor tyrosine kinase isolated from a transforming virus, and identify its ligand.